Brigham and Women's Hospitals

Nephrology

Updated: May 3, 2020

Acute Kidney Injury

Incidence and Pathophysiology

  1. Incidence of AKI in COVID-19 varies widely, but estimates range from 0.5% (Guan et al, NEJM, 2020) to 27% (Diao et al, medRXiv, 2020). The wide range of estimates of AKI incidence may reflect different populations included in studies (e.g. floor vs ICU patients).
  2. The most likely etiology of AKI is acute tubular necrosis (ATN) based on autopsy series from China, but other findings including interstitial inflammation, thrombotic microangiopathy, complement-mediated injury and direct viral infection of tubular cells and podocytes has also been described (Su et al, Kidney int, 2020 and Diao et al, medRXiv, 2020).
  3. There has been a lot of speculation about the role of the renin-angiotensin-aldosterone system and medications that target it on the severity of COVID-19, since angiotensin-converting enzyme 2 (ACE2) is used by SARS-CoV-2 as a functional receptor to enter into cells (including type II pneumocytes and kidney tubular epithelial cells). Data is limited so far but there is no current evidence that use of ACE inhibitors or angiotensin-receptor blockers (ARBs) is associated with worse outcomes in patients with COVID-19 (Mancia et al, NEJM, 2020, Reynolds et al, NEJM, 2020). Please see “ACEI/ARB” section of the Therapeutics chapter for discussion.

Work up:

  1. Monitor serum creatinine and electrolytes at least daily
  1. Studies find variable onset of AKI, from 7 days (Cheng et al, medRxiv, 2020 preprint) to 15 days after illness onset (Zhou et al, Lancet, 2020). Onset of AKI more rapid and severe in patients with underlying CKD (Cheng et al, medRxiv, 2020 preprint)
  1. In patients with AKI, order urine electrolytes (urine Na, urea and Cr) and urinalysis with sediment
  1. Patients may present with proteinuria (44%), hematuria (26.9%) (Cheng et al, medRxiv, 2020 preprint)
  2. For patients with proteinuria, quantify proteinuria with spot urine protein-to-creatinine and albumin-to-creatinine ratios
  1. Consider other common etiologies of AKI that can occur in patients who do not have COVID-19 (e.g. volume depletion, ATN from hypotension, contrast-associated nephropathy, acute interstitial nephritis and urinary tract obstruction)

Management:

  1. Discontinue all medications that can contribute to AKI (e.g. NSAIDs, ACE inhibitors, ARBs, and diuretics in volume depleted patients) and avoid using iodinated contrast with CT imaging as much as possible
  2. Consider a gentle fluid challenge (e.g. 1 liter of isotonic crystalloid fluid) to determine if there is a pre-renal component to AKI, especially in patients with clinical or laboratory signs suggestive of intravascular volume depletion (e.g. hypotension, tachycardia, dry mucous membranes, FENa<1% and/or FEurea<35%).
  1. Be cautious with fluid administration in patients with severe hypoxemia
  1. Consult nephrology for patients with any of the following:
  1. Creatinine clearance <30 ml/min/1.73m2
  2. Oliguria: urine output <500cc/day or <0.5cc/Kg/hour
  3. Volume overload not improving with diuretics
  4. Hyperkalemia (>5.5) not responsive to dietary K restriction and diuretics

Renal Replacement Therapy (RRT)

  1. Estimates for RRT range from 0.8 to 5% of hospitalized patients (Guan et al, NEJM, 2020, Zhou et al, Lancet, 2020) in studies including floor patients. Among critically ill patients in the ICU, need for CRRT has been reported as high as 39% (Chen et al, Lancet, 2020).
  1. Few studies have reported outcomes of RRT. One case series reported that out of 191 patients, 10 received CRRT, and all 10 died (Zhou et al, Lancet, 2020).
  1. The nephrology consult service will determine the need, timing, and modality of renal replacement on a case-by-case basis.
  1. Indications for RRT in COVID-19 patients are the same as the indications for all patients.

Prognosis

  1. Increased serum creatine, BUN, AKI, proteinuria, or hematuria are each independent risk factors for in-hospital death (Cheng et al, medRxiv, 2020 preprint)
  1. In two other studies, non-survivors had higher BUN and creatinine and higher rates of AKI (Wang et al, JAMA, 2020; Yang et al, Lancet Respir Med, 2020).
  2. Another study found that higher BUN and creatinine are associated with progression to ARDS, and higher BUN (though not creatinine) is associated with death (HR 1.06-1.20) (Wu et al, JAMA Intern Med, 2020).
  3. Based on previous data from SARS, AKI was associated with poor prognosis as 91.7% of patients with AKI died (vs 8.8% without AKI, p < 0.0001) (Chu et al, Kidney Int, 2005).